Aaron M Whittaker, Feng Peng, Eric Sirota, Mark McLaughlin, Hongming Li, Charles Orella, Lushi Tan, Wenjun Liu, Thomas P Vickery, Daniel Bishara, Nicholas J Rogus, Jongrock Kong, Cyndi Qixin He, Zhiguo J Song, Kevin M Maloney, Steven Crossley, Xiao Wang, Chaohui Song, Guangxin Shao, Lianjie Li, Aijie Zhao, Lu Chen
A practical and asymmetric synthesis of potent anti-HIV nucleoside MK-8527 is described. The key discoveries are a novel stereoselective dynamic kinetic resolution (DKR) Mitsunobu glycosylation and selective amination of the resulting 2,6-dichloro nucleoside. The new route was successfully demonstrated on the kilogram scale and provided isolated MK-8527 with more than 99% HPLC purity through crystallization.